tbuckley/cabot-search huggingface dataset:
Abstract 12554: Hipsc Derived Cardiomyocytes for Mechanistic, Patient Tailored Treatment in a Novel Mutation Linked to Cpvt
Authors: Noah Goehringer, Harald Stachelscheid, Ibrahim El-Battrawy, Katarzyna Ludwik, Leif-Hendrik Boldt, Abdul Parwani, Burkert Pieske, Frank Heinzel, Felix Hohendanner
Journal: Circulation (2022)

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a disease related to altered ryanodine receptor (RyR) mediated SR Ca 2+ leak and associated with sudden cardiac death in young adults. We recently identified a family with a mixed phenotype of CPVT and long-QT-syndrome (CPVT3*) related to a novel mutation in the trans-2.3-enyol-CoA reductase-like (TECRL) gene. Ventricular arrhythmia burden varies greatly between individual CPVT3* patients. Methods/Results: We generated human induced pluripotent stem cell derived cardiomyocytes (iPSc-CM) from a control and CPVT3* patient to explore underlying mechanisms and individualize pharmacological treatment. iPSc-CM were studied using confocal Ca 2+ imaging (fluo-4). Ca 2+ signaling during excitation-contraction coupling was studied in the presence of different clinically available modulators of RyR mediated SR Ca 2+ leak. In particular, cardiomyocyte function and arrythmias were tested upon addition of the class Ic antiarrhythmic flecainide (10μM), the RyR stabilizer dantrolene (1μM), the betablocker R-Carvedilol (1μM), the kinase inhibitor Rimacalib (10μM) and the RyR-Calstabin interaction stabilizer S107 (10μM). Under baseline conditions, CPVT3* iPSc-CM showed significantly decreased Ca 2+ transient (CaT) amplitudes and increased CaT duration. Upon addition of the beta-agonist isoproterenol (ISO, 100nM), CaT amplitudes and pro-arrhythmogenic Ca 2+ release (i.e. Ca 2+ sparks) significantly increased in CPVT3* as compared to control. All pharmaceuticals altered Ca 2+ signaling in CPVT3* in a substance dependent manner and pro-arrhythmogenic Ca 2+ release was particularly mitigated upon addition of flecainide. Treatment of the CPVT3* patient with flecainide significantly reduced ventricular premature beats as determined by 24 hour holter-ECG monitoring. Conclusion: We quantitatively assessed drugs targeting RyR mediated SR Ca 2+ leak in a CPVT3* patient with a novel TECRL mutation using iPSc-CM. Favorable in-vitro results of flecainide were mirrored in a significant reduction of ventricular arrhythmia in-vivo. Our results underscore the potential of iPSc-CM for the development of patient-tailored treatment in genetic arrhythmia syndromes.
Abstract 12028: Neural Mechanisms of Postoperative Atrial Fibrillation Suppression Using Nanoformulated Calcium Targeting Cardiac Ganglionated Plexi
Authors: Ehsan Jafree, Michael O'Quinn, Rahul Myadam, Brianna Rose, Kenneth Dormer, Kytai T Nguyen, Anindita Das, Mohammed Quader, Vigneshwar KASIRAJAN, Karoly Kaszala, Kenneth A Ellenbogen, Jose Huizar, Alex Y Tan
Journal: Circulation (2022)

Introduction: The neural mechanisms of postoperative atrial fibrillation (POAF) remain unclear. Hypothesis: We hypothesize that injection of left atrial GP with nanoformulated calcium chloride (nCaCl2) causes GP neuroapoptosis, inhibition of sympathetic and vagal nerve activity (SNA, VNA) and consequent suppression of POAF. Methods: In a novel canine model of POAF with serial bilateral thoracotomy surgeries, we assessed ambulatory SNA and VNA before (baseline), 3-days after and 6-weeks after injection of 1ml of nCaCl2 (n=6) or sham (n=3) into each of 4 left atrial GP. We also serially assessed atrial effective refractory period (AERP) and AF vulnerability (AFV) by in-vivo programmed stimulation before and 6 weeks after nCaCl2 treatment. Results: In this POAF model, postoperative atrial electrical remodeling manifests as a reduction in AERP and increase in AFV from baseline (week 0) to postop (week 3) (Table). Subsequent nCaCl2 treatment at week 3 reversed these changes (increased AERP, decreased AFV) at 6 weeks post-treatment, vs persistently decreased AERP and increased AFV in the sham control group. Three days after nCaCl2 treatment, there was a reduction in SNA and VNA vs baseline and increase in mean and standard deviation (SD) RR intervals vs baseline, whereas the sham group demonstrated the opposite changes (increased SNA, decreased mean RR and SDRR vs baseline). At 6-weeks post-treatment, mean and SDRR remained persistently increased whereas SNA remained suppressed vs baseline. In contrast, SNA remained elevated and mean RR decreased vs baseline in the sham group. Histology demonstrated neuronal apoptosis within GP without atrial myocardial infiltration in nCaCl2-treated but not in sham. Conclusions: Modulation of cardiac GP with nanoformulated calcium causes GP neuroapoptosis, which exerts a persistent sympatho- and parasympatholysis across the cardiac neuraxis, promoting reversed atrial electrical remodeling and durable suppression of POAF.
Abstract 12435: A Rare Case of Pericarditis Following Varicella-Zoster Vaccination
Authors: Dominic R Mears, Sandeep S Hothi
Journal: Circulation (2022)

Introduction: We emphasise the role of imaging as illustrated by the case of a 71-year-old male who presented with acute pericarditis one day after receiving a Varicella Zoster Virus (VZV) Vaccination. Although active VZV infection itself is recognised as an uncommon trigger for pericarditis, and myopericarditis following several live attenuated vaccines, its occurrence specifically following VZV vaccination is rare. Case Presentation: This gentleman was previously fit and well prior with no significant comorbidity or drug allergies. Clinically, we suspected VZV vaccine-induced pericarditis in this case due to the short temporal relationship between vaccination and symptom onset and absence of other known infectious and non-infectious causes of pericarditis. This was in addition to characteristic chest pain, fever, sweating, electrocardiogram (clear PR depression and subtle concave ST elevation) and imaging (echocardiography and Cardiac MRI) features. Imaging Results: Pulmonary embolism was excluded by CT pulmonary angiography, but this scan did reveal a large, global pericardial effusion. Prompt transthoracic echocardiogram categorised the pericardial effusion as small and did not show any signs of cardiac tamponade. Cardiac MRI imaging demonstrated a large pericardial effusion but did not show any overt myocardial oedema, inflammation or fibrosis, consistent with a low high-sensitivity troponin I. Interestingly, the MRI did not reveal any convincing pericardial oedema or fibrosis acutely, which might be expected in pericarditis. Transthoracic echocardiography was important in excluding features of tamponade and helped confirm the diagnosis of acute pericarditis by clearly demonstrating the pericardial effusion. A Cardiac MRI was essential in excluding co-existent myocarditis and infarction. Conclusions: Acute pericarditis should be considered in patients presenting with chest pain after receiving the VZV vaccination and patients should be made aware of this rare side effect prior to receiving their vaccination. The patient in this case study responded well to symptomatic treatment with analgesia and colchicine, suggesting that anti-viral therapy is not required for VZV related pericarditis.
Abstract 12215: A Case of Post-Vaccine Myocarditis Mimicking Long Covid
Authors: Eric Hirsch, Leandro Slipczuk, Mark Travin, Renee Moadel, Ulrich P Jorde, Sasha VUKELIC
Journal: Circulation (2022)

Myocarditis is a rare complication following mRNA-based COVID vaccinations. While the risk appears to be greatest in adolescent males, increased rates of myocarditis following COVID vaccination have been documented in both sexes and across multiple age groups.In this case, a 59-year-old woman with history of mild COVID infection developed unexplained fatigue, diminished exercise capacity, and intermittent chest discomfort several days after receiving her first dose of the Pfizer-BioNTech COVID-19 vaccine. She was seen in the emergency department at the onset of symptoms and found to have a dynamic troponin elevation peaking at 177 ng/L. A comprehensive workup including regadenoson stress testing, CT scan of the chest with contrast, and ambulatory cardiac monitoring failed to demonstrate an etiology. She subsequently received a second dose of the COVID-19 vaccine which resulted in worsening cardiopulmonary symptoms that persisted over the next several months. Her symptoms were initially attributed to long COVID, and she was provided supportive care and an SSRI for anxiety. After reevaluation in the Cardiology clinic, the patient underwent cardiac MRI revealing edema in the basal lateral wall and late gadolinium enhancement in a subepicardial distribution, suggestive of myocardial inflammation. She was treated with prednisone 50 mg daily and colchicine 0.6 mg twice daily resulting in resolution of chest pain. A repeat MRI performed two weeks later showed complete resolution of myocardial edema with residual subepicardial LGE in the basal lateral wall consistent with prior myocarditis.This case demonstrates the pitfalls of relying on a diagnosis of ‘long COVID’ to explain concerning cardiac symptoms of uncertain etiology and highlights post-vaccine myocarditis as an important differential in the COVID-19 era. At this time, it is unclear how many patients experience persistent cardiopulmonary symptoms following COVID vaccination and whether a subset of these patients have undiagnosed myocarditis. It is important for clinicians to be alert to the possibility of post-vaccine myocarditis in patients presenting with persistent symptoms following vaccination, regardless of demographic profile.
Abstract 12234: A Three-Dimensional Culture System Composed of Hipsc Derived Cms, Ecs, Smcs, and Cardiac Fibroblasts Promotes Hipsc-cm Maturation
Authors: Asher Kahn-Krell, Danielle Pretorius, Bijay Guragain, Xi Lou, Yuhua Wei, Jianhua Zhang, Aijun Qiao, Yuji Nakada, Timothy J Kamp, Lei Ye, Jianyi J Zhang
Journal: Circulation (2022)

Introduction: Cardiomyocytes (CMs), endothelial cells (ECs), smooth muscle cells (SMCs), and cardiac fibroblasts (CFs) differentiated from human induced-pluripotent stem cells (hiPSCs) are the fundamental components of cell-based regenerative myocardial therapy and can be used as in-vitro models for mechanistic studies and drug testing. However, newly differentiated hiPSC-CMs tend to more closely resemble fetal CMs than the mature CMs of adult hearts, and current techniques for improving CM maturation can be both complex and labor-intensive. Hypothesis: CMs tend to develop a more mature phenotype when cultured as spheroids in a three-dimensional (3D) environment, rather than as two-dimensional monolayers, and the activity of ECs, SMCs, and CFs promote both CM maturation and electrical activity. Methods: hiPSCs were differentiated into CMs (hiPSC-CMs) using a belly dancer shaker in 3D condition and seeded into 96-Well of Nunclon Sphera-Treated, U-Shaped-Bottom Microplate (Thermo Fisher Scientific). hiPSC differentiated endothelial cells (hiPSC-ECs), smooth muscle cells (hiPSC-SMCs), and cardiac fibroblasts (hiPSC-CFs) were added to each well to produce cardiac spheroids. Quantitative polymerase chain reaction (qPCR), western blot, immunostaining, bioenergetics, transmission electron microscopy, field potential, and contractility of cardiac spheroids were characterized. Results: The inclusion of hiPSC-ECs, -SMCs, and CFs in CM spheroids increased spheroid size and improved cell viability. hiPSC-ECs, -SMCs, and -CFs promoted hiPSC-CMs maturation in cardiac spheroids: a. gene expression levels of TNNI3, N-cadherin, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) significantly increased; b. Contractile fibers were better organized and mitochondria were better aligned; c. ATP level, the ratio of NAD:NADH, and cAMP level were greater in cardiac spheroids; d. Field-potential duration and conduction velocity were greater in CMs in cardiac spheroids. Conclusion: we developed a simple and reproducible 3D-culture-based process for generating cardiac spheroids containing more mature hiPSC-CMs in the presence of ECs, SMCs, and CFs.
Abstract 11358: Total Cost of Care in Heart Failure Patients Receiving Parenteral Iron Therapy for Iron Deficiency Anemia: A Retrospective Analysis
Authors: W J Kwong, Kevin Wang, Ralph V Boccia
Journal: Circulation (2022)

Introduction: Iron deficiency (ID) is a common comorbidity in heart failure (HF) patients. This study compared healthcare costs between treatment with ferric carboxymaltose (FCM) and low dose IV iron (LDI) in HF patients with iron deficiency anemia (IDA). Methods: Medical and pharmacy claims from IQVIA PharMetrics ® Plus data were analyzed. Adult patients who received FCM or LDI (i.e iron sucrose, iron dextran, sodium ferric gluconate complex in sucrose) from 2017 to 2019, who had HF and IDA medical claims and were continuously eligible 6 months before (baseline) and 12 months after first (index) IV iron infusion were included. Patients with chronic kidney disease who required dialysis were excluded. Eligible FCM patients were required to receive 2 FCM doses within 21 days of index date. Healthcare resource use and costs for pre- and post-index periods were summarized descriptively. Post-index monthly inpatient, outpatient (excluding IV iron), and total costs for FCM and LDI were compared using generalized linear model with gamma log-link adjusting for pre-index monthly cost, age, gender, year of index treatment and Charlson Comorbidity Index. Results: Data from 3,153 FCM patients and 3,971 LDI patients were analyzed. Unadjusted mean number of outpatient visits increased numerically in the LDI group and unchanged for FCM, whereas ER visits and inpatient admissions decreased numerically for both treatment groups in the post-index period compared to baseline. After adjusting for covariates, post-index monthly inpatient costs [adjusted cost ratio (ACR)= 0.70, p &lt;0.001], outpatient costs (ACR=0.74, p &lt;0.001) and total costs (including IV iron) (ACR = 0.81, p &lt;0.001) were significantly lower for FCM than LDI. Conclusion: Higher acquisition cost of FCM was offset by lower inpatient and outpatient costs in HF patients with IDA receiving FCM than LDI during the 12 months after IV iron treatment, resulting in significantly lower total healthcare costs for FCM compared to LDI.
Abstract 12219: Social Vulnerability and Cardiometabolic Risk Factors in Pregnant Women in the United States
Authors: Kristen Harris, Joseph Reed, Tony Dong, Sadeer Al-Kindi
Journal: Circulation (2022)

Background: In recent years, pregnancy-related mortality rates in the US have increased, with cardiovascular disease accounting for a third of all pregnancy-related mortality. The association between cardiometabolic (CM) health and social determinants of health have not been well understood. Objectives: We sought to investigate the relationship between social vulnerability and prevalence of CM risk factors in pregnant women in the US. Methods: In this cross-sectional analysis, we linked natality files including all pregnancies resulting in live births in the US (aggregated 2016-2020) with county-level social vulnerability index (SVI), a composite metric of social risk factors with four major domains: socioeconomic, household composition/disability, minority status/language, and housing type/transportation. We investigated the association between SVI and its subdomains with county-level prevalence of maternal pre-pregnancy diabetes, pre-pregnancy hypertension, tobacco use, and obesity. Results: A total of 18,953,511 pregnancies were analyzed across 577 counties. All CM risk factors were associated with SVI and/or its 4 subcomponents to varying degrees. Obesity was strongly associated with overall SVI (R=0.52, P&lt;0.001) with an even stronger relationship with socioeconomic vulnerability (R=0.6, P&lt;0.001) and household composition/disability (R=0.66, P&lt;0.001). The rate of pre-pregnancy diabetes was associated with overall SVI (R=0.27, p&lt;0.001), with similar association with socioeconomic vulnerability (R=0.26, P&lt;0.001) and household composition/disability (R=0.28, P&lt;0.001). Chronic hypertension was weakly associated with overall SVI (R=0.15, P&lt;0.001) with similar association with socioeconomic vulnerability (R=0.19, P&lt;0.001) and household composition/disability (R=0.22, P&lt;0.001). Tobacco use was not associated with overall SVI (R=0.034, p=0.41), but was strongly associated with minority status/language (R=-0.71, P&lt;0.001). Conclusion: Social vulnerability and its domains are associated with prevalence of CM risk factors in pregnant women in the US. Further studies are needed to investigate the impact of targeting social determinants of health to improve CM risk and mortality in pregnant women.
Abstract 12244: Loneliness, Social Isolation, and Incident Heart Failure in the Southern Community Cohort Study
Authors: Kaleel Wainwright, Meng Xu, Debra Dixon, Loren Lipworth, Deepak K Gupta
Journal: Circulation (2022)

Introduction: Loneliness and social isolation are associated with worse outcomes among individuals with prevalent heart failure (HF). Less is known regarding loneliness and incident HF, particularly among individuals of low socioeconomic position. Methods: We studied 26,666 Southern Community Cohort Study participants without prevalent HF enrolled between 2002-2009. At enrollment, loneliness was assessed via a 4-level question on the Center for Epidemiologic Studies Depression Scale. Incident HF was ascertained through CMS linkage using ICD-9 (428.x) and ICD-10 (I50.x) claims through 2016. Associations between loneliness and social isolation, e.g., marital status, household size, close friends or relatives, and help in emergency, with incident HF were examined with multivariable Cox regression. Results: The study population was predominantly middle-aged (median 54 years), female (63%), Black (69%), with low annual income (70% &lt; $15,000) and education (92% &lt; college graduate). Individuals reporting greater loneliness tended to be younger, female, with lower income and educational attainment. Over a median 9.8 years follow-up, 7,396 (27.7%) individuals developed HF. In Cox models adjusted for demographics and traditional CV risk factors, greater loneliness significantly associated with increased risk for HF (HR: 1.04, 95% CI: 1.01-1.06), which attenuated following adjustment for education and income (HR 1.02, 95% CI: 0.99-1.04) (Table) without evidence for effect modification by either education or income (p-interaction &gt;0.19 for both). Education and income significantly and inversely associated with incident HF risk while social isolation measures did not. Conclusion: Among individuals of low-socioeconomic position, an association between loneliness or social isolation and incident HF did not persist after adjustment for education and income emphasizing the importance of socioeconomic status as a risk factor for incident HF.
Abstract 12462: Percutaneous Repair of Chronic Aortic Pseudoaneurysm: A Single Center Experience
Authors: Bruce Lewis, Dominick Bufalino, Sorcha Allen, Lucas Burke, Mohammed H Hussein, Rashad Belin, Jeffrey Schwartz
Journal: Circulation (2022)

Introduction: Aortic pseudoaneurysm (AP) is a late complication of aortic repair. Without intervention, it carries a mortality rate up to 61%. Surgical repair has significant in-hospital mortality (6.9-12.6%) and high healthcare costs. Endovascular stent grafting has 15.2% all-cause mortality and 9.3% re-intervention rates. Percutaneous vascular plug/occluder technology emerged as a potentially safer and cheaper alternative to surgical AP closure. We will share our experience with this technology to enhance its success rate, safety, and cost-effectiveness. Methods: We retrospectively reviewed percutaneous AP closure cases with vascular plug/occluder technology published (2005 - 2016) and analyzed them alongside those performed at our institution (2017 - 2019). Results: We identified 40 cases of percutaneous AP closure with vascular plug/occluder technology in the literature and 10 performed at our institution. Our patients had a 1.9-day average length of stay with 100% successful targeted AP closure compared to 92% in the literature group. Over a 12-month median follow-up period (range 3-47 months), AP demonstrated stable or reduced sac size in 6 (60%) of our cases but increased in 4 (40%), necessitating surgical intervention. Literature cases had a 2-month median follow-up period with a 65% success rate. Death occurred in 40% of our patients from non-AP-related causes and in 8% of the literature group from AP closure-related complications. The cost per procedure was $49,580, which is hypothetically less than open surgical repair. Conclusion: Our experience shows a viable option for vascular plug/occluder technology in percutaneous AP repair, given its initial safety and cost-effectiveness. Our results highlight the critical role of follow-up imaging in identifying AP expansion and the need for further intervention. The high non-aorta-related mortality seen in follow-up emphasizes the high-risk nature of the population due to co-morbidities. .
Abstract 12030: Myocardial Extracellular Volume in Patients With Type 2 Diabetes
Authors: Annemie S Bojer, Martin Heyn Soerensen, Peter Gaede, Per L Madsen
Journal: Circulation (2022)

Introduction: Myocardial interstitial fibrosis expands the extracellular volume (ECV) and is in patients with type 2 diabetes implicated in the development of heart failure. ECV can be determined with gadolinium-contrast magnetic resonance imaging. Hypothesis: We investigated if known risk factors for cardiovascular disease were associated with increased ECV in patients with type 2 diabetes. Methods: 296 patients with type 2 diabetes and 21 healthy sex and age-matched controls were included in a cross-sectional magnetic resonance imaging study. The influence of risk factors on ECV was investigated by multiple regression analysis. Results: Controls and patients with type 2 diabetes without complications had similar ECV (27.1±2.1% vs. 27.9±2.6%, p=0.2). Compared to patients without, ECV was significantly increased in patients with 1≥ complication (29.0±3.3%, p=0.02). Both in univariable analysis and after multivariable adjustment, ischemic heart disease, autonomic neuropathy and active smoking were associated with increased levels of ECV. Active smoking exhibited the largest effect size (ß=2.0%-point 95%CI 0.7 to 3.3). Former smokers had similar ECV than never smokers. Albuminuria and systolic blood pressure were inversely associated with ECV in multivariable analysis but after adjustment for medication suspected to affect ECV the association to albuminuria was no longer significant (p=0.1). There was a trend toward SGLT2i treatment being associated with reduced ECV (-0.8% 95%CI -1.7 to 0.06, p=0.067). Conclusions: Patients with complications to diabetes have increased ECV not seen in patients without. Active but not former smoking was highly associated with increased ECV but also Ischemic heart disease, and autonomic neuropathy.